In human medicine, it has hitherto been customary practice to send samples of body fluids, e.g. blood, plasma or urine, for analysis to a specialized clinical laboratory possessing the necessary technical equipment and trained staff. Clinical chemical parameters of particular interest are, for example:
pH,
concentrations of electrolytes, such as Li.sup.+, Na.sup.+, K.sup.+, Ca.sup.2+, Mg.sup.2+, C1.sup.-, HCO.sub.3 .sup.- and NH.sub.3 (NH.sub.4 .sup.+),
concentrations of dissolved gases, notably oxygen and carbon dioxide (conventionally reported in the form of partial pressures, e.g. pO.sub.2, pCO.sub.2),
haemoglobin concentration,
concentrations of metabolic factors, such as glucose, creatinine, urea (BUN), uric acid, lactic acid, pyruvic acid, ascorbic acid, phosphate, protein, bilirubin, cholesterol, triglycerides, phenylalanine and tyrosine,
concentrations of enzymes, such as lactic acid dehydrogenase (LDH), lipase, amylase, choline esterase, alkaline phosphatase, acid phosphatase, alanine amino transferase (ALAT), aspartate amino transferase (ASAT) and creatinine kinase (CK), and
concentrations of ligands, such as antibodies and nucleotide fragments.
In the past, clinical chemical analysis systems have tended to be large in size, expensive and complex to operate, and in general only relatively large medical institutions have been able to afford the purchase, operation and maintenance of such systems. Smaller hospitals, clinics, general practitioners etc., usually have had to employ centralized commercial or hospital laboratories for clinical chemical analyses, leading to unavoidable delays in the procedure.
Since abnormal values of certain clinical chemical parameters are indicative of serious danger to health, the rapid and reliable determination of clinical chemical parameters in general is of crucial importance for proper and effective medical treatment. Furthermore, quite apart from the acute aspects of medical treatment, it is clearly an advantage, both for patients from a psychological viewpoint and for medical staff from an administrative viewpoint, that clinical analysis results are accessible as quickly as possible.
Thus, increasing demands for reduction in costs, more rapid turnover, greater decentralisation and increased staff flexibility in clinical chemical analysis have provided an incentive for the development of easy-to-use, easy-to-maintain, reliable, relatively cheap, compact and, if possible, portable equipment, based in part on discardable components, for the bedside measurement of those characteristics of chemical species which constitute fundamental clinical chemical parameters of body fluids.
Equipment based in part on disposable components may also be of great value in numerous non-medical analytical applications where the ability to carry out decentralised or field analyses is of importance. Examples of such applications are the determination of pH, colour and concentrations of chemical species such as chloride, nitrite, nitrate, sulfate and phosphate in relation to control of the quality of bodies of water used for domestic supplies, and on-site analyses of the contents of process vessels, e.g. in fermentation processes such as the production of beers and wines, in sugar refining and in industrial syntheses.
PCT applications WO 85/02257, WO 85/04719 and WO 86/05590, U.S. Pat. No. 4,436,610, U.S. Pat. No. 4,225,410 and European application EP 0189316, disclose apparatuses, all of which comprise a disposable measuring device and an analyzer, suitable for bedside clinical chemical analyses, notably of blood samples. European patent EP 0012031 discloses a method and apparatus for measuring a chemical characteristic of a liquid, in particular for measuring the pH of a blood sample. The preferred embodiments of the measuring devices disclosed in the first five of the above mentioned sources are intended for discardment after a single use, whereas a preferred embodiment disclosed in EP 0189316 and embodiments disclosed in EP 0012031 are intended to be disposed of after repeated use. In each of these devices the sensor or sensors responsive to the chemical species, and the chamber(s) or passage(s) in which the sensor or sensors are exposed to a calibration fluid or a sample fluid remain fixed with respect to the housing or support of the measuring device as a whole.
British application GB 2 183 041 discloses apparatus comprising an analyzer and a measuring device for analyzing an undiluted body fluid, the measuring device comprises an ion-selective or enzymatic sensing electrode which is mounted on a probe, the probe being movable to transfer the sensing electrode between an open-ended reference wash cell and a sample cup bearing the body fluid specimen to be analyzed. The measuring device disclosed is intended for prolonged repeated use and is rather complex in its construction.
As will be described in detail in the following, the present invention concerns, inter alia, methods using discardable measuring devices for measuring a characteristic which is a function of the concentration of one or more chemical species in a sample fluid, for example a body fluid, the measurement entailing movement of a sensor relative to a sample fluid chamber containing a sample fluid and/or relative to a chamber containing a fluid for conditioning the sensor (e.g. calibrating the sensor response), or movement of said sample fluid chamber and/or said conditioning fluid chamber relative to a sensor. As will become clear from the following, this principle offers a number of advantages in connection with measurements using discardable measuring devices.